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10 notes available
1 Last Minute Review 2 Polyneuropathies 3 Mononeuropathies & Plexopathies 4 Motor Neuron Disease 5 Myasthenia Gravis & NMJ Disorders 6 Inflammatory Myopathies 7 Muscular Dystrophies 8 Channelopathies & Metabolic Myopathies 9 Neuromuscular Emergencies 10 EMG/NCS Patterns
Clinical › Neuromuscular

Polyneuropathies

Polyneuropathies

What You'll Learn

  • GBS: acute ascending paralysis, albuminocytological dissociation, sural sparing on NCS; treat with IVIg or PE — NOT steroids; monitor for respiratory failure (20/30/40 rule)
  • CIDP: chronic (≥8 weeks) proximal + distal symmetric weakness with demyelinating NCS; unlike GBS, steroids DO work (along with IVIg and PE)
  • MMN: pure motor, asymmetric, upper-limb predominant; conduction block at non-entrapment sites; anti-GM1 IgM in ~50%; IVIG only (steroids and PLEX worsen or are ineffective)
  • Nodal/paranodal antibody neuropathies (anti-NF155, anti-CNTN1, anti-NF186, anti-CASPR1) are classified separately from CIDP per EFNS/PNS 2021 and often respond poorly to IVIg, especially IgG4 NF155/CNTN1/CASPR1 phenotypes; rituximab is commonly used (largely observational evidence); antibody subclass and optimal treatment vary by target
  • hATTR amyloidosis: bilateral CTS + progressive sensorimotor + cardiomyopathy. U.S. hATTR polyneuropathy drugs = TTR knockdown (patisiran, vutrisiran, inotersen, eplontersen). TTR stabilizers (tafamidis, acoramidis) are FDA-approved for ATTR cardiomyopathy in the U.S., NOT polyneuropathy (tafamidis has non-U.S. neuropathy approval in some regions)
  • CMT1A (PMP22 duplication) is the most common hereditary neuropathy — uniform slowing without conduction block distinguishes hereditary from acquired demyelinating neuropathies
  • Diabetic neuropathy: distal symmetric polyneuropathy is most common; diabetic amyotrophy = lumbosacral radiculoplexopathy; pupil-sparing CN III = diabetic mononeuropathy
  • Small fiber neuropathy: burning pain, normal NCS, diagnose with skin punch biopsy (reduced IENFD)
  • Vasculitic neuropathy: mononeuritis multiplex pattern; sural nerve biopsy shows necrotizing vasculitis; treat with steroids + cyclophosphamide
  • POEMS syndrome: Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes — lambda restriction in >95% of cases (kappa POEMS rare but reported); look for sclerotic bone lesions
HighYield Pearls
  • GBS / AIDP: ascending symmetric weakness + areflexia days–weeks after Campylobacter jejuni (#1) or respiratory infection; CSF albuminocytologic dissociation by week 1; demyelinating NCS with prolonged distal latencies, slow CV, temporal dispersion, conduction block; treat with IVIG OR PLEX (equally effective — NOT steroids, NOT combined); monitor FVC/NIF using 20/30/40 rule (FVC <20 mL/kg, MIP weaker than −30, MEP <40) → intubate; watch for autonomic instability (leading ICU cause of death)
  • Miller-Fisher syndrome: ophthalmoplegia + ataxia + areflexia; anti-GQ1b in >90%; usually self-limited — IVIG/PLEX only if severe or GBS overlap (Bickerstaff if altered consciousness)
  • CIDP: symmetric proximal AND distal weakness + sensory loss + areflexia progressing ≥8 weeks; demyelinating NCS in ≥2 nerves; elevated CSF protein; first-line = IVIG, steroids, OR PLEX (unlike GBS, steroids work); relapsing-remitting or progressive course
  • MMN: asymmetric, pure motor, upper-limb predominant weakness in named-nerve distributions with NO sensory loss; conduction block at non-entrapment sites; anti-GM1 IgM in ~50%; IVIG only — steroids and PLEX are CONTRAINDICATED (paradoxical worsening); rituximab as add-on
  • Anti-MAG / DADS neuropathy: elderly patient with distal sensory > motor demyelinating neuropathy + IgM kappa MGUS + prominent sensory ataxia + tremor; markedly prolonged terminal motor latency (low TLI); rituximab is treatment of choice — IVIG/steroids fail
  • POEMS: Polyneuropathy + Organomegaly + Endocrinopathy + Monoclonal gammopathy (overwhelmingly lambda-restricted; kappa rare but reported) + Skin changes; elevated VEGF; mixed demyelinating + axonal neuropathy; treat the plasma cell disorder (autologous SCT or radiation if solitary plasmacytoma)
  • CMT1A: most common inherited neuropathy — PMP22 duplication at 17p11.2, AD, demyelinating; pes cavus + stork legs + hammertoes + tremor in childhood/teens; uniform slowing WITHOUT conduction block (vs acquired); HNPP = PMP22 deletion (reciprocal)
  • Vasculitic neuropathy: stepwise, painful, asymmetric mononeuritis multiplex; sural nerve biopsy = epineurial necrotizing vasculitis (diagnostic); causes include ANCA vasculitis, PAN (hepatitis B), cryoglobulinemia (HCV); treat with steroids + cyclophosphamide or rituximab
  • Diabetic neuropathies: distal symmetric polyneuropathy (most common; treat painful DSPN with duloxetine, pregabalin, gabapentin, or TCAs per AAN/AAPMR); diabetic amyotrophy = severe asymmetric proximal LE pain + weakness + weight loss in older diabetic, may benefit from steroids/IVIG; pupil-sparing CN III = diabetic mononeuropathy
  • B12 deficiency: subacute combined degeneration (dorsal columns + lateral corticospinal tracts) + axonal sensorimotor neuropathy + macrocytic anemia; elevated MMA AND homocysteine (MMA more specific); treat with IM cobalamin. Copper deficiency mimics SCD (post-gastric bypass or zinc excess) — check ceruloplasmin/copper, replace copper, stop zinc
  • Amyloid neuropathy (hATTR): bilateral CTS + small-fiber/autonomic dysfunction + cardiomyopathy; Val30Met most common (Portugal/Sweden/Japan); Val122Ile in African-Americans; Congo red apple-green birefringence. For U.S. hATTR polyneuropathy: TTR knockdown (patisiran, vutrisiran, inotersen, eplontersen). TTR stabilizers (tafamidis, acoramidis) are U.S. cardiomyopathy drugs (tafamidis has non-U.S. neuropathy use). AL amyloid → chemotherapy ± autoSCT
🔍 Quick ReferenceClinical · EMG/NCS + CSF / labs · Antibody / gene / pathology
Clinical phenotype
  • Ascending symmetric weakness + areflexia after gastroenteritis → GBS / AIDP
  • Ophthalmoplegia + ataxia + areflexia → Miller-Fisher syndrome
  • Chronic ≥8-week symmetric proximal AND distal weakness with areflexia → CIDP
  • Asymmetric pure motor weakness in named-nerve distributions, no sensory loss → MMN
  • Asymmetric, multifocal demyelinating sensory and motor weakness with conduction block → Lewis-Sumner / MADSAM
  • Stepwise, painful, asymmetric sensorimotor deficits (mononeuritis multiplex) → vasculitic neuropathy
  • Elderly man with distal sensory ataxia + tremor + IgM MGUS → anti-MAG / DADS neuropathy
  • Subacute combined degeneration (dorsal column + corticospinal) + macrocytic anemia → B12 deficiency (or copper if zinc excess / post-gastric bypass)
  • Pes cavus + hammertoes + “stork-leg” atrophy + high-steppage gait in a teen → CMT (most often CMT1A)
  • Bilateral CTS + progressive sensorimotor neuropathy + cardiomyopathy + autonomic dysfunction → hATTR amyloidosis
  • Charcot foot + stocking-glove sensory loss → diabetic distal symmetric polyneuropathy
  • Severe proximal LE pain + weakness + weight loss in older diabetic → diabetic amyotrophy (lumbosacral radiculoplexus neuropathy)
EMG/NCS + CSF / labs
  • Albuminocytologic dissociation (high protein, normal cells) in CSF → GBS or CIDP
  • Sural-sparing pattern (absent upper-limb SNAPs, preserved sural SNAP) → AIDP
  • Demyelinating features (prolonged distal latency, slow CV, prolonged F-waves, temporal dispersion, conduction block) in ≥2 nerves → CIDP
  • Motor conduction block at non-entrapment sites with NORMAL sensory NCS → MMN
  • Low CMAPs, normal SNAPs, normal velocities → AMAN; reduced CMAPs AND SNAPs → AMSAN
  • Markedly prolonged terminal motor latency (low terminal latency index) → anti-MAG neuropathy
  • Elevated VEGF + IgG/IgA-lambda M-spike + sclerotic bone lesions → POEMS syndrome
  • Elevated MMA + homocysteine → B12 deficiency; low ceruloplasmin/copper + high zinc → copper deficiency myeloneuropathy
  • Uniform CV slowing without conduction block → hereditary demyelinating neuropathy (CMT1)
  • SPEP/UPEP + immunofixation + free light chains positive → screen for MGUS, myeloma, AL amyloid, POEMS, Waldenström
Antibody / gene / pathology
  • Anti-GM1 / anti-GD1a IgG → AMAN (Campylobacter molecular mimicry)
  • Anti-GQ1b (>90%) → Miller-Fisher syndrome (and Bickerstaff overlap)
  • Anti-MAG IgM kappa → anti-MAG / DADS neuropathy
  • Anti-GM1 IgM (~50%) → MMN
  • Anti-NF155 (tremor, refractory) / anti-CNTN1 (nephrotic syndrome) / anti-NF186 / anti-CASPR1 → autoimmune nodopathies (IgG4 → rituximab)
  • Preceding Campylobacter, EBV, CMV, Zika, or SARS-CoV-2 → GBS trigger
  • PMP22 duplication (17p11.2) → CMT1A; PMP22 deletion → HNPP
  • MPZ → CMT1B; GJB1 / Connexin-32 → CMT-X1 (males more severe; CNS lesions possible)
  • MFN2 → CMT2A (most common axonal CMT); SH3TC2 → CMT4C
  • TTR mutation (Val30Met, Val122Ile) → hATTR amyloidosis
  • Onion-bulb formations on nerve biopsy → CMT1 or CIDP (repeated de-/remyelination)
  • Epineurial necrotizing vasculitis on sural biopsy → vasculitic neuropathy
  • Congo red apple-green birefringence under polarized light → amyloid neuropathy
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